The farnesylation of a C-terminal cysteine residue is a required post- translational modification that allows Ras proteins to associate with cellular membranes and to have cell-transforming activity. Since mutations in Ras proteins have been associated with Ca. 30% of human cancers, inhibitors of protein farnesylation are potential cancer therapeutics. Protein farnesyl transferase (PFTase) is the enzyme that farnesylates eukaryotic proteins, including Ras. A great deal of research has been directed at finding inhibitors of PFTase, although little is known about the structure of the enzyme or how it binds substrates and metals. In an effort to gain a better understanding of the structural elements of PFTase and to locate the substrate/metal binding sites, the metal binding sites will be mapped by protein cleavage with Fenton-type chemistry. This will be accomplished by selectively replacing Mg2+ with the redox active metal Fe2+ and oxidatively cleaving the protein. Separately, Zn2+ will be selectively replaced with Cu2+ and the protein will be oxidatively cleaved. These techniques will allow the protein residues comprising both metal binding sites to be mapped and will allow a model of the protein structure to be proposed. This information, combined with the current knowledge of PFTase, should allow the rational design of improved PFTase inhibitors and could ultimately lead to potential cancer therapeutics.